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hypothetical benzodiazepine mixed agonist / inverse agonist

Raihiar

Raihiar

Greenlighter
Joined
Feb 1, 2011
Messages
43
Hello fellow bluelighters :)

A question kept spooking around in my head, ever since i read a post in another thread (don't remember which).

Lets assume there is a compound, that acts as a potent agonist on 4 of the 5 subrezeptors of the Benzo-receptor, and acts as inverse agonist (or maybe antagonist) on the one that is mainly responsible für the amnesia.
Any guesses, how that would feel / work?

And as a related question: if I were physically addicted to a 'balanced' benzo (maybe like diazepam, i'd think), and ingested the compund mentioned in my first question - what do you think would happen?

I hope i posted this in the right subforum, but it seemed appropriate.. if somewhere else is better, feel free to move the thread and excuse my mistake :)
 
Raihiar said:
Hello fellow bluelighters :)

A question kept spooking around in my head, ever since i read a post in another thread (don't remember which).

Lets assume there is a compound, that acts as a potent agonist on 4 of the 5 subrezeptors of the Benzo-receptor, and acts as inverse agonist (or maybe antagonist) on the one that is mainly responsible für the amnesia.
Any guesses, how that would feel / work?

And as a related question: if I were physically addicted to a 'balanced' benzo (maybe like diazepam, i'd think), and ingested the compund mentioned in my first question - what do you think would happen?

I hope i posted this in the right subforum, but it seemed appropriate.. if somewhere else is better, feel free to move the thread and excuse my mistake :)
Click to expand...

The alpha-1 subunit is responsible for amnesia, sedation and anticonvulsant effects.

So the answer for your first question is that you would experience anti-anxiety effects and muscle relaxation but not amnesia or sedation.

The answer to your second question is that you would probably experience a seizure if you were addicted to diazepam and then took a drug that acted as an inverse agonist at alpha-1 subunits.
 
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How does "pure" anti-anxiety looks like? I always thought anti-anxiety and sedation are the same, that you cant be anxiety free without being sedated. Seems it is wrong thinking...
 
Renald said:
How does "pure" anti-anxiety looks like? I always thought anti-anxiety and sedation are the same, that you cant be anxiety free without being sedated. Seems it is wrong thinking...
Click to expand...

They are actually not the same. Often a single compound will produce both effects so they seem to be linked, but it is possible to synthesize benzodiazepine ligands that are selective for particular alpha subunits.

Several pharmaceutical companies have tried to develop benzodiazepine ligands that are preferentially anxiolytic or sedating . The results have been mixed. That was exactly the reason why z-drugs like zolpidem were developed -- they were intended to be sedating but not anxiolytic. To some degree that is the case, but they only have limited selectivity and hence they also produce some degree of anxiolytic effects.


http://www.ncbi.nlm.nih.gov/pubmed/15926867
 
ok, from what i got from Serotonin2A's and Clubcard's answers is, that i had some misunderstanding of both the GABA A-Receptor and the BZD-binding site..

so purely anti-amnesia is not possible without risk of seizure... damn :/
well, (i hope) i learned something today, so the question wasn't a total waste of time for everyone involved :)

thanks a lot for the fast and understandable replies :)

i have a few other more or less related questions, but it's late here and i'm tired from an exhaustive day, so i'll call it a day and post the questions later on.
(read: prepare to be bombarded with some semi-informed ideas and seek shelter somewhere safe =D)
 
serotonin2A said:
They are actually not the same. Often a single compound will produce both effects so they seem to be linked, but it is possible to synthesize benzodiazepine ligands that are selective for particular alpha subunits.

Several pharmaceutical companies have tried to develop benzodiazepine ligands that are preferentially anxiolytic or sedating . The results have been mixed. That was exactly the reason why z-drugs like zolpidem were developed -- they were intended to be sedating but not anxiolytic. To some degree that is the case, but they only have limited selectivity and hence they also produce some degree of anxiolytic effects.

http://www.ncbi.nlm.nih.gov/pubmed/15926867
Click to expand...

What is the goal pharmaceutical companies are trying to achieve by developing sedating but non-anxiolytic drugs? Surely having anxiolytic effects cannot be bad?
 
aced126 said:
What is the goal pharmaceutical companies are trying to achieve by developing sedating but non-anxiolytic drugs? Surely having anxiolytic effects cannot be bad?
Click to expand...

It potentially increases their abuse potential. Benzodiazepines are often abused for their anxiolytic effects, as opposed to making people fall asleep.
 
i can't say it without being really sure, but from what i remember (haha...) zopiclone and to a lesser extent zolpidem were VERY amnesic when i used them (about once every two weeks) in therapeutic doses and without recreational use in mind.
Esp. Zopiclone wiped my mind clean without fail for the following ~24 hrs. after ingestion
 
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